title: Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.
abstract: During retina development, retinal progenitor cell (RPC) proliferation and differentiation are regulated by complex inter- and intracellular interactions. Bone marrow mesenchymal stem cells (BMSCs) are reported to express a variety of cytokines and neurotrophic factors, which have powerful trophic and protective functions for neural tissue-derived cells. Here, we show that the expanded RPC cultures treated with BMSC-derived conditioned medium (CM) which was substantially enriched for bFGF and CNTF, expressed clearly increased levels of nuclear receptor TLX, an essential regulator of neural stem cell (NSC) self-renewal, as well as betacellulin (BTC), an EGF-like protein described as supporting NSC expansion. The BMSC CM- or bFGF-treated RPCs also displayed an obviously enhanced proliferation capability, while BMSC CM-derived bFGF knocked down by anti-bFGF, the effect of BMSC CM on enhancing RPC proliferation was partly reversed. Under differentiation conditions, treatment with BMSC CM or CNTF markedly favoured RPC differentiation towards retinal neurons, including Brn3a-positive retinal ganglion cells (RGCs) and rhodopsin-positive photoreceptors, and clearly diminished retinal glial cell differentiation. These findings demonstrate that BMSCs supported RPC proliferation and neuronal differentiation which may be partly mediated by BMSC CM-derived bFGF and CNTF, reveal potential limitations of RPC culture systems, and suggest a means for optimizing RPC cell fate determination in vitro.
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xia
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.forename: Ni
authors.initials: N
authors.lastname: Ni
authors.forename: Junzhao
authors.initials: J
authors.lastname: Chen
authors.forename: Yamin
authors.initials: Y
authors.lastname: Hu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Deng
authors.forename: Jing
authors.initials: J
authors.lastname: Ji
authors.forename: Jibo
authors.initials: J
authors.lastname: Zhou
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
authors.forename: Ping
authors.initials: P
authors.lastname: Gu
mesh_terms: D000818:Animals; D002452:Cell Count; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D012160:Retina / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D009414:Nerve Growth Factors